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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #255026
Title: Methylselenol, a selenium metabolite, plays common and different roles in cancerous colon HCT116 cell and noncancerous NCM460 colon cell proliferation

Author
item Zeng, Huawei
item Briske Anderson, Mary
item WU, MIN - University Of North Dakota
item MOYER, MARY - Incell Corporation

Submitted to: Nutrition and Cancer
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/3/2011
Publication Date: 2/10/2012
Citation: Zeng, H., Briske Anderson, M.J., Wu, M., Moyer, M.P. 2012. Methylselenol, a selenium metabolite, plays common and different roles in cancerous colon HCT116 cell and noncancerous NCM460 colon cell proliferation. Nutrition and Cancer. 64(1):128-135.

Interpretive Summary: Epidemiological evidence indicates that selenium status is inversely associated with cancer risk, and results from intervention studies show that high Se intakes effectively reduce the risk of mammary, prostate, lung, colon, and liver cancer. Our previous data demonstrated that Se-enriched broccoli decreases intestinal tumorigenesis in multiple intestinal neoplasia in a mouse model. Methylselenol has been hypothesized to be a critical selenium (Se) metabolite for anticancer activity in vivo. However, the molecular mechanism(s) for these effects still remain poorly characterized. In this study, our data demonstrate that methylselenol’s stronger potential of inhibiting colon cancer proliferation, and survival signals in cancerous colon HCT116 cells when compared with noncancerous colon cells is a critical mechanism by which selenium exerts its anticancer property. The information will be useful for scientists and health-care professionals who are interested in using selenium as a nutrient and cancer prevention.

Technical Abstract: Methylselenol has been hypothesized to be a critical selenium (Se) metabolite for anticancer activity in vivo. To determine differential chemopreventive effects of methylselenol on colon cancer cells versus colon noncancerous cells, colon-cancer-derived HCT-116 cells and noncancerous colonic NCM460 cells were exposed to methylselenol. The submicromolar methylselenol was generated by incubating methionase with seleno-Lmethionine. Methylselenol exposure inhibited cell growth and led to an increase in the G1 and G2 fractions with a concomitant drop in the S-phase, and an induction of apoptosis in HCT116 (up to 3.2 fold of the control), but to a much lesser extent in NCM460 colon cells (up to 1.4 fold of the control). The examination of mitogen-activated protein kinase (MAPK) and c-Myc signaling status revealed that methylselenol inhibited the phosphorylation of extracellular-regulated kinase1/2 (ERK1/2) and p38 MAPK, and the expression of c-Myc in HCT116 cells, but to a much lesser extent in NCM460 cells. Interestingly, methylselenol also inhibits the phosphorylation of both Src and FAK survival signals in HCT116 cells. In sharp contrast, methylselenol up-regulated the phosphorylation of both Src and FAK survival signals in NCM460 cells. Taken together, our data demonstrate that methylselenol’s stronger potential of inhibiting colon cancer proliferation, and survival signals in cancerous colon HCT116 cells when compared with noncancerous colon cells is a critical mechanism by which selenium exerts its anticancer property.